Ruvim Izikson, MD, MPH

October 20th, 2021

Some information contained within this slide deck pertains to investigational agents or uses that have not been 

approved by the FDA. No conclusions regarding safety and efficacy should be drawn for such agents or uses.

Phase II, open-label study to assess the safety and immunogenicity of Fluzone® 

High-Dose Quadrivalent (Influenza Vaccine), 2021–2022 Formulation and a third 

dose of mRNA-1273 COVID-19 vaccine (Moderna) administered either 

concomitantly or singly in adults 65 years of age and older previously vaccinated 

with a 2-dose schedule of mRNA-1273 vaccine 

Study Code: QHD00028 

https://clinicaltrials.gov/ct2/show/NCT04969276

In partnership with:

• The Biomedical Advanced Research and Development Authority, part of the office of the Assistant 

Secretary for Preparedness and Response at the U.S. Department of Health and Human Services

• Moderna, Inc.
Rationale for vaccine selection and study group

2

• Adults 65 years of age and older are a critical priority for influenza and 

COVID-19 immunizations due to the risk of severe complications 

• Based on the COVID-19 vaccine primary series timing and strategy, older 

adults are most likely eligible for COVID-19 boosters and their annual 

influenza vaccine during the same window of time

• This creates the risk that many get vaccinated only for one or the other; with priority on 

COVID-19, influenza is more likely the missed vaccine

• QIV-HD is the most frequently administered influenza vaccine to individuals 

65 years of age and older in the US1

• 100μg mRNA-1273 vaccine dose was selected based on projected 

regulatory expectations at the time of study start

1. Internal calculations by Sanofi based on IQVIA database of total flu vaccines administered from 8/20-3/21 in adults 65+. Study 

details and information maintained by Sanofi
• Descriptive study 

with ~300 

participants (100 per 

group)

• Randomized, open 

label, conducted in 

the US

• Participants received 

2 doses of mRNA-

1273 vaccine at least 

5 months before 

enrollment

• mRNA-1273 vaccine 

booster dose (100μg)

• QIV-HD 2021-2022 

formulation (240μg)

• Offered to Group 3 

participants at D22 as 

part of routine medical 

care 

Study Design

3
Study Timeline

4

12May2021

Internal study 

endorsement

11Jun2021

FDA protocol 

submission

25Jun2021

FDA protocol 

approval

01Jul2021

IRB approval

16Jul2021

First Visit First 

Subject

05Aug2021

First Visit Last 

Subject

31Aug2021

Last Visit Last 

Subject 

(D22+W3)

13Sep2021

Database Lock

20Sep2021

Laboratory results

28Sep2021

Statistical analysis

05Oct2021

Interim Clinical 

Study Report
Demographics by treatment group 

5
Demographics by treatment group 

6
Study objectives

7

Safety

• To describe the safety profile of QIV-HD and mRNA-1273 vaccine administered 

concomitantly or singly

• Solicited injection site reactions and systemic reactions occurring through 7 days after 

injection

• Unsolicited systemic adverse events through 21 days after vaccination

• Serious adverse events (SAEs), adverse events of special interest (AESIs) and 

medically-attended adverse events (MAAEs) through 6 months after vaccination

Immunogenicity

• To describe the immune response elicited by QIV-HD administered concomitantly or 

singly, in each study intervention group

• To describe the immune response elicited by mRNA-1273 vaccine administered 

concomitantly or singly, in each study intervention group 
Summary of solicited reactions (Day 1 - 8)

8

Grade 3: A type of adverse event that interrupts usual 

activities of daily living, or significantly affects clinical 

status, or may require intensive therapeutic 

intervention.

Grade 3: > 100 mm
Solicited injection site reactions (Day 1 - 8)

9

Grade 3: A type of adverse event that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive 

therapeutic intervention.

Grade 3: > 100 mm

0

10

20

30

40

50

60

70

80

90

100

Injection site

pain

Axillary swelling Axillary

tenderness

Injection site

erythema

Injection site

swelling

Injection site

induration

Injection site

bruising

%

QIV-HD (COAD)

QIV-HD

mRNA-1273 (COAD)

mRNA-1273

Grade 3
Solicited systemic reactions (Day 1 - 8)

10

0

10

20

30

40

50

60

70

80

90

100

Fever Headache Malaise Myalgia Arthralgia Shivering Fatigue Nausea Vomiting

QIV-HD + mRNA-1273

QIV-HD

mRNA-1273

Grade 3

Grade 3: A type of adverse event that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive 

therapeutic intervention.

Grade 3: ≥ 39.0°C or ≥ 102.1°F
Unsolicited adverse events through 21 days

11
Medically-attended adverse events through day 22

Medically Attended AE (MAAE): 12

A new onset or a worsening of a condition that prompts to seek unplanned medical advice at a physician’s office or Emergency Department
Safety summary (Solicited Reactions)

13

• Injection site reactions

• QIV-HD: injection site reaction frequency was similar whether the vaccine was administered concomitantly 

or singly.

• mRNA-1273: injection site reaction frequency was similar whether vaccine was administered 

concomitantly or singly.

• Injection site pain was the most frequently reported injection site reaction for both vaccines. The frequency of injection site pain 

tended to be lower following injection of QIV-HD.

• The frequency of Grade 3 injection site reactions tended to be lower following injection of QIV-HD compared to mRNA-1273.

• Systemic reactions

• Fatigue was most frequently reported in all treatment groups. The frequency was similar in the coadministration group and mRNA-1273 group and lower in QIV-HD group.

• Frequency of Grade 3 systemic reactions was similar in the co-administration group and mRNA-1273 

group and lower in QIV-HD group.
Safety summary

14

• No SAEs, AESIs or deaths.

• No AEs leading to study discontinuation.

MAAEs

• One participant in the mRNA-1273 (alone) group experienced a MAAE assessed 

as related (PT: muscle spasms).

Unsolicited AEs and ARs

• The frequency of unsolicited AEs and ARs was similar across treatment groups

o Most unsolicited AEs were systemic in nature.

o In co-administration group and QIV-HD group, one participant in each reported a Grade 3 unsolicited AE.

o One participant in the QIV-HD (alone) group with an immediate unsolicited AR (PT: dizziness).
Study Objectives

15

Safety

• To describe the safety profile of QIV-HD and mRNA-1273 vaccine administered 

concomitantly or singly

• Solicited injection site reactions and systemic reactions occurring through 7 days after 

injection

• Unsolicited systemic adverse events through 21 days after vaccination

• Serious adverse events (SAEs), adverse events of special interest (AESIs) and 

medically-attended adverse events (MAAEs) through 6 months after vaccination

Immunogenicity

• To describe the immune response elicited by QIV-HD administered concomitantly or singly, 

in each study intervention group

• To describe the immune response elicited by mRNA-1273 vaccine administered 

concomitantly or singly, in each study intervention group 
Geometric mean titer of influenza HA antibody response 

(pre- and post- vaccination), by strain and group

0.0

100.0

200.0

300.0

400.0

500.0

600.0

700.0

A/H1N1 A/H3N2 B/Yam B/Vic

GMT

Group 1 (QIV-HD+mRNA-1273; pre dose) Group 1 (QIV-HD+mRNA-1273; post dose)

Group 2 (QIV-HD only; pre dose) Group 2 (QIV-HD only; post dose)

Group 3 (mRNA-1273 only; pre dose) Group 3 (mRNA-1273 only; post dose)

Abbreviation: GMT=geometric mean titer
Influenza HA antibody titer ≥1:40 (pre and post vaccination), by 

strain and group

0.0%

20.0%

40.0%

60.0%

80.0%

100.0%

A/H1N1 A/H3N2 B/Yam B/Vic

Group 1 (QIV-HD+mRNA-1273; pre dose) Group 1 (QIV-HD+mRNA-1273; post dose)

Group 2 (QIV-HD only; pre dose) Group 2 (QIV-HD only; post dose)

Group 3 (mRNA only-1273; pre dose) Group 3 (mRNA-1273 only; post dose)

HAI titer ≥ 40 (1/dil) on D01 and 21 days after injection of QIV-HD (D22)
Seroconversion rate of influenza HA antibody response, by strain 

and by group

A/H1N1 A/H3N2 B/Yam B/Vic

Group 1 (QIV-HD+mRNA-1273) 68.8% 43.8% 17.7% 30.2%

Group 2 (QIV-HD only) 72.1% 47.7% 20.9% 24.4%

Group 3 (mRNA-1273 only) 0.0% 0.0% 1.0% 1.0%

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

100.0%

SCR

Abbreviation: SCR=seroconversion rate

Definition: titer < 10 [1/dil] at D01 and post-vaccination titer ≥ 40 [1/dil] at D22, or titer ≥ 10 [1/dil] at D01 and a ≥ 4-

fold-rise in titer [1/dil] at D22
Antibody response to SARS-CoV-2 by ELISA

Abbreviation: GMC=geometric mean concentration; GMCR=geometric mean concentration ratio

Group 1

(QIV-HD+mRNA-1273) Group 2 (QIV-HD only) Group 3 (mRNA-1273only)

Pre dose GMC (primary axis) 565 462 552

Post dose GMC (primary axis) 7634 395 7904

1

10

100

1000

10000

GEOMETRIC MEAN CONCENTRATION 

(LOG SCALE)

GMCR (post vs pre dose): 

13.70 (95% CI 11.20-16.80)

GMCR (post vs pre dose): 

0.88 (95% CI 0.75-1.03)

GMCR (post vs pre dose): 

14.20 (95% CI 12.00-16.90)

565 (479; 666) 462 (382; 560) 552 (461; 662)

7634 (6445; 9042) 395 (311; 502) 7904 (6883; 9077)
Immunogenicity summary

20

HAI immune response

• All 3 treatment groups demonstrated similar GMT levels at baseline

• At day 22, the co-administration group and QIV-HD group demonstrated similar 

GMT levels, proportions of participants with titers ≥ 1:40, and seroconversion 

rates for each influenza strain.

SARS-CoV-2 immune response

• All 3 treatment groups demonstrated similar GMC levels at baseline.

• At day 22, the co-administration group and mRNA-1273 group demonstrated 

similar GMC levels and proportions of participants with ≥ 2- and ≥ 4-fold-rise of 

antibody titers.
Overall interpretation

21

The QHD00028 study results demonstrate that QIV-HD and mRNA-1273 

vaccine (100μg) can be administered safely together without evidence 

of immunogenicity interference, supporting existing co-administration 

recommendations of COVID-19 and influenza vaccines.
Much thanks for the collaboration and support from:

22

Sanofi Pasteur

• US: L. Perez, A. Collins, T. Washington, D. Ecker, M. Stirr, D. Divito, B. D’Arienzo, J. Olsommer, J. Soreth-Harman, N. Lupinsky, 

H. Kabler, M. Martin, C. Rizzo, M. Greenberg

• Global: S. Samson, M. Fournier, S. Wagué, P. Bourron, C. Salamand, C. Tabar, JS Bolduc, N. Sater, R. Fernando, S. Yandle, A. 

Pandey, M. Bonaparte, K Yin, A. Pallez, N. Otmani, H. Velasco, A. Meramo, A. Shrestha, Y. Davis, I. Gregoire, S. Orlowski, D. 

McDonough, H. Tekfi, AI Fontvieille, L. Urcuyo, Q. Deng, R. Wang, S. Marszalek, T. Mallett-Moore, M. Lardon, B. Germain, A. 

Trebaul, M. Bayet, S. Samson, B. Coudsy, J. Nealon, R. Harris, C. Guzman, K. Yin, M. Loiacono, S. Pépin, I. De Bruijn, D. 

Greenberg, I. Bruyère

BARDA

• C. Oshansky, R. Donis, R. Gorman, K. Lu, B. Yeh, C. Pavetto, E. Mcgurrin 

Moderna

• H. Bennett, J. Vanas, A. Sutherland, D. Manzo, A. Figueroa, B. Leav, M. Rossi, W. Saroian, C. Crocker, B. Kuter, J. Miller
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